Premium
Activity of sulfur‐containing intermediate metabolites of spironolactone
Author(s) -
McInnes Gordon T,
Asbury Michael J,
Shelton John R,
Harrison Ian R,
Ramsay Lawrence E,
Venning Geoffrey R,
Clarke Joan M
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.48
Subject(s) - spironolactone , chemistry , fludrocortisone , pharmacology , endocrinology , medicine , biochemistry , heart failure , hydrocortisone
The renal antimineralocorticoid activity of single administrations of 2 sulfur‐containing compounds, which are thought to be intermediate metabolites of spironolactone, was assessed in healthy subjects. They were each active in reversing the urinary electrolyte changes induced by fludrocortisone for 2 to 10 hr after dosing, but only the 7 α‐thiomethyl derivative exhibited activity in the period 12 to 16 hr after treatment. The activity of both drugs was less than that of spironolactone. Taking urinary log 10 Na/K as the best index of antimineralocorticoid activity, the potencies of the intermediates relative to spironolactone were 0.26 (95% confidence limits, 0.12 to 0.49) for 7 α‐thio‐spirolactone and 0.33 (95% confidence limits, 0.15 to 0.62) for 7 α‐thiomethyl‐spirolactone in the period 2 to 10 hr after medication. We conclude that these minor sulfur‐containing intermediate metabolites of spironolactone are unlikely to contribute significantly to the renal antimineralocorticoid activity of spironolactone. Clinical Pharmacology and Therapeutics (1980) 27, 363–369; doi: 10.1038/clpt.1980.48